1. Field
One or more embodiments of the present invention relate to novel benzothiazole derivative compounds effective for cancer treatment, and more particularly, to a benzothiazole derivative compound, a use of the benzothiazole derivative compound for cancer treatment, and a use of the benzothiazole derivative compound as a radiation sensitizer for cancer treatment.
2. Description of the Related Art
Even with the recent sharp increase in cancer incidence due to rapid industrial development, global ecosystem changes, and dietary changes, cancer is still an incurable disease due to the yet unidentified incidence mechanism of cancer. Anticancer drugs in current use may be largely classified into biological drugs, such as enzymatic drugs or vaccines, pure synthetic drugs, and drugs derived from natural products. Anticancer drugs may exhibit various pharmacological actions depending on the types of cancer and have various side effects due to toxicity, and thus, may be problematic in cancer treatment. Anticancer drugs may effectively suppress the growth of cancer cells, but also have toxicity to normal cells. Due to this, many scholars have done research to develop a more effective anticancer drug having minimum toxicity to normal cells.
Lung cancer is the second most prevalent cancer, next to gastric cancer, and has been first in mortality among other cancers since the year 2000, due to a poor prognosis. Lung cancer may be histologically classified into small-cell lung cancer or non-small cell lung cancer. Chemotherapy and radiotherapy are recommended for small-cell lung cancer, and radical lumpectomy is known as the best treatment for non-small cell lung cancer. Lung cancer may have a difficulty in local tumor control, and may include micro-metastatic cancer cell that are likely undetectable by diagnostic imaging. Accordingly, local radiotherapy alone on a lung may lead to metastasis to other remote organs, with a 5-year survival rate of less than 10%. Accordingly, a various combinations of radiotherapy with chemotherapy have been used to prevent the recurrence of cancer in remote organs and have been found to be more effective than radiotherapy only.
Peroxisome proliferator activated receptors (PPARs) which are nuclear receptors belonging to the steroid-thyroid-retinoid receptor superfamily are transcription factors of which activities are regulated by various ligands. PPARs are also key factors to regulate sugar and lipid metabolisms, and are also known to regulate cell division, cell differentiation, and cell death in various tissues. Activation of PPAR is known to exhibit anticancer activity in various cancers.
Thiazolidinediones as a diabetes treatment drug, including troglitazone (TGZ), ciglitazone, rosiglitazone, or pioglitazone, are synthetic PPARγ agonists. Reportedly, TGZ is known to have a cytotoxic effect on various human cancers of the colon (Non-patent document 1), the breast (Non-patent document 2), the liver, the lungs, the kidneys, and the prostate.
It has been suggested that the activation of PPAR β/δ ameliorates lung cancer. High-affinity synthetic ligand for PPAR β/δ, such as L165041, was found to suppress cell proliferation in human lung cancer (Non-patent document 3) and to exacerbate lung cancer in a transgenic mouse lacking the gene expression of PPAR β/δ (Non-patent document 4).
The expression of PPAR γ prognosis was found to be reduced in lung cancer patients with a poor prognosis (Non-patent document 8). The activation of PPAR γ by an endogenous agonist or a synthetic agonist was found to suppress the growth of lung cancer (Non-patent document 5). The treatment of non-small cell lung cancer with PPAR γ active materials was reported to induce apoptosis and differentiation (Non-patent document 6). Ciglitazone was reported to suppress tumors derived from A-549 cells in nude mice (Non-patent document 7). Diabetes patients administered with thiazolidinedione known as PPAR γ agonist to treat diabetes were found to have a remarkably low likelihood of developing lung cancer (Non-patent document 8). The reaction of PPAR-γ ligands was found to protect the body from lung cancer (Non-patent documents 9 and 10).
PPAR-γ ligands are known to have anticancer functions through dependent or independent pathways on PPAR-γ, and in particular, the latter was found to be related with lung cancer (Non-patent document 11).